| Literature DB >> 30863922 |
Vylyny Chat1,2,3, Robert Ferguson1,2,3, Danny Simpson1,2,3, Esther Kazlow1,2,3, Rebecca Lax1,2,3, Una Moran1,3,4,5, Anna Pavlick3,4, Dennie Frederick6, Genevieve Boland6, Ryan Sullivan6, Antoni Ribas7, Keith Flaherty6, Iman Osman1,3,4,5, Jeffrey Weber1,3,4, Tomas Kirchhoff8,9,10.
Abstract
Immune-checkpoint inhibition (ICI) treatments improve outcomes for metastatic melanoma; however, > 60% of treated patients do not respond to ICI. Current biomarkers do not reliably explain ICI resistance. Given the link between ICI and autoimmunity, we investigated if genetic susceptibility to autoimmunity modulates ICI efficacy. In 436 patients with metastatic melanoma receiving single line ICI or combination treatment, we tested 25 SNPs, associated with > 2 autoimmune diseases in recent genome-wide association studies, for modulation of ICI efficacy. We found that rs17388568-a risk variant for allergy, colitis and type 1 diabetes-was associated with increased anti-PD-1 response, with significance surpassing multiple testing adjustments (OR 0.26; 95% CI 0.12-0.53; p = 0.0002). This variant maps to a locus of established immune-related genes: IL2 and IL21. Our study provides first evidence that autoimmune genetic susceptibility may modulate ICI efficacy, suggesting that systematic testing of autoimmune risk loci could reveal personalized biomarkers of ICI response.Entities:
Keywords: Autoimmunity; Germline variants; Immune-checkpoint inhibition; Melanoma
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Year: 2019 PMID： 30863922 PMCID： PMC6531317 DOI： 10.1007/s00262-019-02318-8
Source DB: PubMed Journal: Cancer Immunol Immunother ISSN： 0340-7004 Impact factor: 6.968